A metabolite screen identifies acetate to promote proliferation of AMPK-deficient AML cells. (A) Metabolomics analysis with mass spectrometry revealed that AMPK-deficient AML cells had decreased metabolites in glycolysis and tricarboxylic acid cycle, as well as amino acids and nucleotides pathways (n = 9). (B) A schematic of a screening strategy using metabolite supplementation to rescue the defective proliferation of AMPK-deficient AML cells. (C) Results from the metabolite screening identified acetate to rescue AMPK-deficient AML. Wild-type (WT) or AMPK-deficient (KO) AML cells were cultured in the presence of the indicated compound for 72 hours, and cell proliferation was monitored by a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. 2-deoxyglucose (2DG), an inhibitor of glycolysis, was included as a control. Fold changes in signals were normalized against those from wells supplemented with phosphate-buffered saline. (D) WT or AMPK KO AML cells were cultured with (Ac) or without (phosphate-buffered saline) 2 mM acetate supplementation, and cell proliferation was monitored (n = 3). All data represent mean ± standard deviation; *P < .05; **P < .01; ***P < .001 by Student’s t-test.